Validation of memory assessment in the Starmaze task: Data from 14 month-old APPPS1 mice and controls.

This article describes navigation data of 14 month-old APPPS1 and C57Bl6 in the Starmaze task. These data were acquired as positive controls of memory deficit in a model of the familial form of Alzheimers's disease (see Schmitt et al., Flexibility as a marker of early cognitive decline in humanized Apolipoprotein E ε4 (ApoE4) mice, Neurobiol Aging, 2021). They were acquired in a reduced version of the Starmaze environment and accompanied by a number of acquisitions in different control groups at 6 and 14 months to assess the robustness of the procedure and its associated memory scores. These data illustrate the extraction of a variety of navigation scores (including search strategy, spatial learning and memory) and provide a reference of navigation data in the Starmaze task for healthy 6-month-old controls, normal aging and a model of pathological memory deficit.

Flexibility as a marker of early cognitive decline in humanized apolipoprotein E ε4 (ApoE4) mice.

To test the hypothesis that ApoE4 may be involved in cognitive deficits associated with aging, we investigated the impact of APOE4 status and aging on the flexibility and memory components of spatial learning in mice. Young adult (6 months) and middle-aged (14 months) ApoE4, ApoE3 and C57BL/6 male mice were tested for flexibility in an aquatic Y-maze, and for spatio-temporal memory acquisition in the Starmaze. Our results revealed a flexibility deficit of the 6-month-old ApoE4 mice compared to controls. However, this deficit was not associated with spatio-temporal memory deficit at the same age. Importantly, the ApoE4 flexibility deficit did not increase with age, nor turn into memory deficit, or was able to predict individual variations of memory performance at 14 months. By contrast, control ApoE3 mice showed a decline of flexibility at 14 months resulting in performance similar to that of ApoE4. Overall, our results suggest that ApoE4 could be associated with an acceleration of the flexibility decrease otherwise observed in normal aging.

Do relevant shear forces appear in isokinetic shoulder testing to be implemented in biomechanical models?

Isokinetic dynamometers measure joint torques about a single fixed rotational axis. Previous studies yet suggested that muscles produce both tangential and radial forces during a movement, so that the contact forces exerted to perform this movement are multidirectional. Then, isokinetic dynamometers might neglect the torque components about the two other Euclidean space axes. Our objective was to experimentally quantify the shear forces impact on the overall shoulder torque, by comparing the dynamometer torque to the torque computed from the contact forces at the hand and elbow. Ten healthy women performed isokinetic maximal internal/external concentric/eccentric shoulder rotation movements. The hand and elbow contact forces were measured using two six-axis force sensors. The main finding is that the contact forces at the hand were not purely tangential to the direction of the movement (effectiveness indexes from 0.26 ±â€¯0.25 to 0.54 ±â€¯0.20), such that the resulting shoulder torque computed from the two force sensors was three-dimensional. Therefore, the flexion and abduction components of the shoulder torque measured by the isokinetic dynamometer were significantly underestimated (up to 94.9%). These findings suggest that musculoskeletal models parameters should not be estimated without accounting for the torques about the three space axes.

Neuroprotective effects of M826, a reversible caspase-3 inhibitor, in the rat malonate model of Huntington's disease.

1. Caspases, key enzymes in the apoptosis pathway, have been detected in the brain of HD patients and in animal models of the disease. In the present study, we investigated the neuroprotective properties of a new, reversible, caspase-3-specific inhibitor, M826 (3-([(2S)-2-[5-tert-butyl-3-[[(4-methyl-1,2,5-oxadiazol-3-yl)methyl]amino]-2-oxopyrazin-1(2H)-yl]butanoyl]amino)-5-[hexyl(methyl)amino]-4-oxopentanoic acid), in a rat malonate model of HD. 2. Pharmacokinetic and autoradiography studies after intrastriatal (i.str.) injection of 1.5 nmol of M826 or its tritiated analogue [(3)H]M826 indicated that the compound diffused within the entire striatum. The elimination half-life (T(1/2)) of M826 in the rat striatum was 3 h. 3. I.str. injection of 1.5 nmol of M826 10 min after malonate infusion induced a significant reduction (66%) in the number of neurones expressing active caspase-3 in the ipsilateral striatum. 4. Inhibition of active caspase-3 translated into a significant but moderate reduction (39%) of the lesion volume, and of cell death (24%), 24 h after injury. The efficacy of M826 at inhibiting cell death was comparable to that of the noncompetitive NMDA receptor antagonist MK801. 5. These data provide in vivo proof-of-concept of the neuroprotective effects of reversible caspase-3 inhibitors in a model of malonate-induced striatal injury in the adult rat.